A cloud model target damage effectiveness assessment algorithm based on spatio-temporal sequence finite multilayer fragments dispersion

To solve the problem of target damage assessment when fragments attack target under uncertain projectile and target intersection in an air defense intercept,this paper proposes a method for calculating target damage probability leveraging spatio-temporal finite multilayer fragments distribution and the target damage assessment algorithm based on cloud model theory.Drawing on the spatial dispersion characteristics of fragments of projectile proximity explosion,we divide into a finite number of fragments distribution planes based on the time series in space,set up a fragment layer dispersion model grounded in the time series and intersection criterion for determining the effective penetration of each layer of fragments into the target.Building on the precondition that the multilayer fragments of the time series effectively assail the target,we also establish the damage criterion of the perforation and penetration damage and deduce the damage probability calculation model.Taking the damage probability of the fragment layer in the spatio-temporal sequence to the target as the input state variable,we introduce cloud model theory to research the target damage assessment method.Combining the equivalent simulation experiment,the scientific and rational nature of the proposed method were validated through quantitative calculations and comparative analysis.

Scale effect removal and range migration correction for hypersonic target coherent detection

The detection of hypersonic targets usually confronts range migration(RM)issue before coherent integration(CI).The traditional methods aiming at correcting RM to obtain CI mainly considers the narrow-band radar condition.However,with the increasing requirement of far-range detection,the time bandwidth product,which is corresponding to radar’s mean power,should be promoted in actual application.Thus,the echo signal generates the scale effect(SE)at large time bandwidth product situation,influencing the intra and inter pulse integration performance.To eliminate SE and correct RM,this paper proposes an effective algorithm,i.e.,scaled location rotation transform(ScLRT).The ScLRT can remove SE to obtain the matching pulse compression(PC)as well as correct RM to complete CI via the location rotation transform,being implemented by seeking the actual rotation angle.Compared to the traditional coherent detection algorithms,Sc LRT can address the SE problem to achieve better detection/estimation capabilities.At last,this paper gives several simulations to assess the viability of ScLRT.

Novel miR-490-3p/hnRNPA1-b/PKM2 axis mediates the Warburg effect and proliferation of colon cancer cells via the PI3K/AKT pathway

BACKGROUND Heterogeneous ribonucleoprotein A1(hnRNPA1)has been reported to enhance the Warburg effect and promote colon cancer(CC)cell proliferation,but the role and mechanism of the miR-490-3p/hnRNPA1-b/PKM2 axis in CC have not yet been elucidated.AIM To investigate the role and mechanism of a novel miR-490-3p/hnRNPA1-b/PKM2 axis in enhancing the Warburg effect and promoting CC cell proliferation through the PI3K/AKT pathway.METHODS Paraffin-embedded pathological sections from 220 CC patients were collected and subjected to immunohistochemical analysis to determine the expression of hnRNPA1-b.The relationship between the expression values and the clinicopathological features of the patients was investigated.Differences in mRNA expression were analyzed using quantitative real-time polymerase chain reaction,while differences in protein expression were analyzed using western blot.Cell proliferation was evaluated using the cell counting kit-8 and 5-ethynyl-2’-deoxyuridine assays,and cell cycle and apoptosis were detected using flow cytometric assays.The targeted binding of miR-490-3p to hnRNPA1-b was validated using a dual luciferase reporter assay.The Warburg effect was evaluated by glucose uptake and lactic acid production assays.RESULTS The expression of hnRNPA1-b was significantly increased in CC tissues and cells compared to normal controls(P<0.05).Immunohistochemical results demonstrated significant variations in the expression of the hnRNPA1-b antigen in different stages of CC,including stage I,II-III,and IV.Furthermore,the clinicopathologic characterization revealed a significant correlation between hnRNPA1-b expression and clinical stage as well as T classification.HnRNPA1-b was found to enhance the Warburg effect through the PI3K/AKT pathway,thereby promoting proliferation of HCT116 and SW620 cells.However,the proliferation of HCT116 and SW620 cells was inhibited when miR-490-3p targeted and bound to hnRNPA1-b,effectively blocking the Warburg effect.CONCLUSION These findings suggest that the novel miR-490-3p/hnRNPA1-b/PKM2 axis could provide a new strategy for the diagnosis and treatment of CC.

Preliminary study on the protective effect of electroacupuncture Neiguan acupoint pretreatment on rats with myocardial ischemia-reperfusion injury:role of the miR-214-3p/NCX1 axis

Background:Ischemia-reperfusion can worsen myocardial damage and increase the risk of death.Studies have revealed that ischemic preconditioning provides the best endogenous protection against myocardial ischemia-reperfusion injury(MIRI),and the principle of electroacupuncture(EA)preconditioning is comparable to that of myocardial ischemic preconditioning adaption.Our earlier research demonstrated that EA pretreatment inhibits the expression of calmodulin-dependent protein kinase IIδ(CaMKIIδ),sodium/calcium exchanger 1(NCX1),and cyclophilin D,hence providing protection against MIRI.However,the exact mechanism is still unknown.The expression of NCX1 mRNA is directly regulated by microRNA-214(miR-214).Moreover,it suppresses the levels of CaMKIIδand cyclophilin D.Whether these variables contribute to EA preconditioning to improve MIRI needs to be investigated,though.This study aimed to preliminarily determine whether EA pretreatment ameliorates MIRI by modulating the miR-214-3p/NCX1 axis.Methods:We used a rat MIRI model to investigate the effect of EA pretreatment on MIRI and the expression of miR-214-3p.In addition,adenovirus injection inhibited miR-214-3p expression in the rat MIRI model,and the influence of EA pretreatment towards MIRI was observed in the context of blocked miR-214-3p expression.Both the myocardial histological abnormalities and the alterations in the ST segment of the rat electrocardiogram were analyzed.NCX1 mRNA,cyclophilin D,and CaMKIIδexpression levels were also analyzed.Results:EA pretreatment improved MIRI.In rats with MIRI,EA administration increased miR-214-3p expression while decreasing NCX1 mRNA,cyclophilin D,and CaMKIIδproteins in cardiac tissues.The beneficial effect of EA pretreatment against MIRI was reversed,coupled with elevated levels of NCX1 mRNA,cyclophilin D,and CaMKIIδprotein expression,when an adenovirus injection disrupted the expression of miR-214-3p.Conclusions:Our findings preliminarily show that EA pretreatment inhibits the expression of NCX1 mRNA,cyclophilin D,and CaMKIIδproteins via miR-214-3p,hence exerting MIRI protection.

Harmful Effects of MSG on Function of Hypothalamus-Pituitary-Target Gland System

It has been demonstrated that neonatal administration of monosodium glutamate (MSG) results in a clearly defined lesion of the arcuate nucleus (AN) of the hypothalamus.The present study shows that fat was accumulated in the abdomen of male rats treated with MSG; weights of the body, pituitary and testis were lower, 6-EP content in hypothalamus decreased while L-EnK content increased, serum LH, FSH, TSH, GH and TS levels all decreased in varying degrees while serum PRL level significantly increased. The cAMP content lowered in pituitary, but nor in testes; clear histological changes occurred in testicular tissue; Se-GSH-Px activity in both testis and adrenal gland lowered while LPO level significantly increased. Both Se-GSH-Px activity and LPO level in liver increased.These results indicate that MSG is harmful to the function of the hypothalamus-pituitarytarget system of neonatal rats

Simulation of Isotopic Angular Effects under Ion Bombardment of a^(92)Mo-^(100)Mo Target

Under 5 keV Ar ion bombardment of a 92Mo-100Mo target, we have investigated isotopic angular effects by means of the static and the dynamic Monte Carlo programs. Our calculated results are in quantitative agreement with the measured and other calculated results. The conclusion consistences among theories. simulations and measurements are also discussed.

Yield Increasing and Quality Improving Effects of Smash-ridging Method("4453" Effects) and Its Potential in Benefiting the Nation and the People

Yuan Longping proposed that smash-ridging technology could be extend-ed widely nationwide. ln the research, smash-ridging technology reconstruct cultiva-tion layers with loose soils in agricultural fields, creating ＂4453＂ effects, as fol ows： ＂Four increases＂ include to increase loosen soil quantity in cultivation layers, soil nutri-ents use, ＂water pool＂ in soils, and ＂oxygen pool＂ in soils. Four reductions are to reduce soil erosion, carbon emission, salt content and heavy metal in soils. Five resistances refer to improve crop resistance capacity in terms of drought, high tem-perature, lower temperature, disease and lodging. Three improvements indicate to enhance photosynthetic efficiency over 10%, yield in 10%-30% and quality over 5%. lt is researched that without additional chemical fertilizer, yield could increase by 10% by labor force, animal, tractor or smash-ridging machine. What’s more, by smash-ridging cultivation, the depth can be 20 times or higher compared with tractor cultivation, with looser soils. lt is estimated that if smash-ridging cultivation is applied once in agricultural lands in China, present soil layers can be twice as deep as present. Specifical y, the thickness of loose soil-layers could be extended from 10-18 cm at present to 25-35 cm, and natural rainfal would increase by 40 bil ion cm3. After vitalization of soil nutrients, chemical fertilizer would decrease by 7 bil ion kg, and the increased c rops would feed more than 300 mil ion population as per yield at 7 50 kg/hm2.

圆锥-球缺组合药型罩战斗部侵彻双层水间隔靶板

为提升聚能战斗部毁伤性能,基于组合药型罩战斗部的起爆机理,设计一种圆锥-球缺组合药型罩聚能战斗部及双层水间隔靶板结构,建立该战斗部侵彻双层水间隔靶板的物理模型,进行数值模拟计算,根据计算结果加工战斗部及靶板的1∶3缩比模型样机,展开相应试验,为设计全尺寸战斗部样机奠定了基础。试验结果表明:该战斗部侵彻含水夹层目标时具有独特的优势,对目标的破坏效应显著增强。

Lactoferrin modification of berberine nanoliposomes enhances the neuroprotective effects in a mouse model of Alzheimer’s disease

Previous studies have shown that berberine has neuroprotective effects against Alzheimer’s disease,including antagonizing tau phosphorylation,and inhibiting acetylcholinesterase activity and neural cell apoptosis.However,its low bioavailability and adverse reactions with conventional administration limit its clinical application.In this study,we prepared berberine nanoliposomes using liposomes characterized by low toxicity,high entrapment efficiency,and biodegradability,and modified them with lactoferrin.Lactoferrin-modified berberine nanoliposomes had uniform particle size and high entrapment efficiency.We used the lactoferrin-modified berberine nanoliposomes to treat a mouse model of Alzheimer’s disease established by injection of amyloid-beta 1-42 into the lateral ventricle.Lactoferrin-modified berberine nanoliposomes inhibited acetylcholinesterase activity and apoptosis in the hippocampus,reduced tau over-phosphorylation in the cerebral cortex,and improved mouse behavior.These findings suggest that modification with lactoferrin can enhance the neuroprotective effects of berberine nanoliposomes in Alzheimer’s disease.

激光光动力疗法联合靶向治疗在晚期贲门-胃底癌中的应用效果

目的:观察激光光动力疗法(LPDT)联合靶向治疗在晚期贲门-胃底癌(CFGC)中的应用效果。方法:选取2020年4月—2022年5月安阳市中医院收治的62例晚期CFGC患者作为研究对象。根据随机数表法将其分为对照组和观察组,各31例。观察组给予靶向治疗联合LPDT,对照组给予靶向治疗。比较两组治疗后食管梗阻程度、近期疗效、不良反应、生存质量,随访3个月、6个月、9个月、12个月生存率。结果:治疗后,观察组食管梗阻程度显著优于对照组,差异有统计学意义(P<0.05)。观察组总有效率为93.55%,明显高于对照组的74.19%,差异有统计学意义(P<0.05)。两组不良反应发生率比较,差异无统计学意义(P>0.05)。观察组生存质量改善率为61.29%,明显高于对照组的35.48%,差异有统计学意义(P<0.05)。观察组治疗后12个月生存率为58.06%,显著高于对照组的32.26%,差异有统计学意义(P<0.05)。结论:LPDT联合靶向治疗可改善晚期CFGC梗阻症状,提高近期疗效,并有助于延长生存期,改善患者生存质量。

花椒热风-微波组合干燥失水特性研究

花椒热风干燥降速期水分含量低,水分扩散慢,导致热风干燥耗时长。为提高干燥效率,并通过热风与微波组合干燥,分别进行热风干燥、微波干燥和热风-微波组合干燥实验,探究不同干燥参数对花椒失水特性的影响,以确定合理的干燥转换临界点和最优组合干燥模型,并将傅里叶准则数(F_(0))引入Fick第二扩散定律方程,求解有效水分扩散系数(D_(eff))。研究结果表明:热风和微波单独干燥时,升高风温风速和增加微波功率均有利于缩短干燥时间;热风-微波组合干燥花椒时,热风段转微波段的最佳目标含水率即为热风干燥的临界点含水率(65%(w.b)),且高热风温度和高微波功率均可使微波干燥段获得高失水速率;热风-微波组合干燥花椒热风段和微波段对应的最优模型分别为Wang and Singh模型和Page模型,D_(eff)范围分别为1.908×10^(-9)~3.547×10^(-9)m^(2)/s和1.883×10^(-8)~3.321×10^(-8)m^(2)/s。热风-微波组合干燥方式能够显著提高干燥效率,促进花椒内部水分扩散,干燥模型可为优化干燥工艺和设计干燥设备提供理论依据。

An Air Defense Weapon Target Assignment Method Based on Multi-Objective Artificial Bee Colony Algorithm

With the advancement of combat equipment technology and combat concepts,new requirements have been put forward for air defense operations during a group target attack.To achieve high-efficiency and lowloss defensive operations,a reasonable air defense weapon assignment strategy is a key step.In this paper,a multi-objective and multi-constraints weapon target assignment(WTA)model is established that aims to minimize the defensive resource loss,minimize total weapon consumption,and minimize the target residual effectiveness.An optimization framework of air defense weapon mission scheduling based on the multiobjective artificial bee colony(MOABC)algorithm is proposed.The solution for point-to-point saturated attack targets at different operational scales is achieved by encoding the nectar with real numbers.Simulations are performed for an imagined air defense scenario,where air defense weapons are saturated.The non-dominated solution sets are obtained by the MOABC algorithm to meet the operational demand.In the case where there are more weapons than targets,more diverse assignment schemes can be selected.According to the inverse generation distance(IGD)index,the convergence and diversity for the solutions of the non-dominated sorting genetic algorithm III(NSGA-III)algorithm and the MOABC algorithm are compared and analyzed.The results prove that the MOABC algorithm has better convergence and the solutions are more evenly distributed among the solution space.

Design and operation strategies of the system for destroying time-sensitive target based on system effectiveness

To improve the effect of destroying time-sensitive target （TST）, a method of operational effectiveness evaluation is presented and some influential factors are analyzed based on the combat flow of system for destroying TST. Considering the possible operation modes of the system, a waved operation mode and a continuous operation mode are put forward at first. At the same time, some relative formulas are modified. In examples, the influential factors and operation modes are analyzed based on the system effectiveness. From simulation results, some design and operation strategies of the system for destroying time sensitive targets are concluded, which benefit to the improvement of the system effectiveness.

Flow behavior in microchannel made of different materials with wall slip velocity and electro-viscous effects

In a microfluidic system, flow slip velocity on a solid wall can be the same order of magnitude as the average velocity in a microchannel. The flow-electricity interaction in a complex microfluidic system subjected to joint action of wall slip and electro-viscous effect is an important topic. This paper presents an analytic solution of pressuredriven liquid flow velocity and flow-induced electric field in a two-dimensional microchannel made of different materials with wall slip and electro-viscous effects. The Poisson- Boltzmann equation and the Navier-Stokes equation are solved for the analytic solutions. The analytic solutions agree well with the numerical solutions. It was found that the wall slip amplifies the fow-induced electric field and enhances the electro-viscous effect on flow. Thus the electro-viscous effect can be significant in a relatively wide microchannel with relatively large kh, the ratio of channel width to thickness of electric double layer, in comparison with the channel without wall slip.

Excellent effects and possible mechanisms of action of a new antibody–drug conjugate against EGFR-positive triple-negative breast cancer

Background:Triple-negative breast cancer(TNBC)is the most aggressive subtype and occurs in approximately 15%–20%of diagnosed breast cancers.TNBC is characterized by its highly metastatic and recurrent features,as well as a lack of specific targets and targeted therapeutics.Epidermal growth factor receptor(EGFR)is highly expressed in a variety of tumors,especially in TNBC.LR004-VC-MMAE is a new EGFR-targeting antibody–drug conjugate produced by our laboratory.This study aimed to evaluate its antitumor activities against EGFR-positive TNBC and further studied its possible mechanism of antitumor action.Methods:LR004-VC-MMAE was prepared by coupling a cytotoxic payload(MMAE)to an anti-EGFR antibody(LR004)via a linker,and the drug-to-antibody ratio(DAR)was analyzed by HIC-HPLC.The gene expression of EGFR in a series of breast cancer cell lines was assessed using a publicly available microarray dataset(GSE41313)and Western blotting.MDA-MB-468 and MDA-MB-231 cells were treated with LR004-VC-MMAE(0,0.0066,0.066,0.66,6.6 nmol/L),and the inhibitory effects of LR004-VC-MMAE on cell proliferation were examined by CCK-8 and colony formation.The migration and invasion capacity of MDA-MB-468 and MDA-MB-231 cells were tested at different LR004-VCMMAE concentrations(2.5 and 5 nmol/L)with wound healing and Transwell invasion assays.Flow cytometric analysis and tumorsphere-forming assays were used to detect the killing effects of LR004-VC-MMAE on cancer stem cells(MDA-MB-468 and MDA-MB-231 cells).The mouse xenograft models were also used to evaluate the antitumor efficacy of LR004-VC-MMAE in vivo.Briefly,BALB/c nude mice were subcutaneously inoculated with MDA-MB-468 or MDAMB-231 cells.Then they were randomly divided into 4 groups(n=6 per group)and treated with PBS,naked LR004(10 mg/kg),LR004-VC-MMAE(10 mg/kg),or doxorubicin,respectively.Tumor sizes and the body weights of mice were measured every 4 d.The effects of LR004-VC-MMAE on apoptosis and cell cycle distribution were analyzed by flow cytometry.Western blotting was used to detect the effects of LR004-VC-MMAE on EGFR,ERK,MEK phosphorylation and tumor stemness marker gene expression.Results:LR004-VC-MMAE with a DAR of 4.02 were obtained.The expression of EGFR was found to be significantly higher in TNBC cells compared with non-TNBC cells(P<0.01).LR004-VC-MMAE inhibited the proliferation of EGFRpositive TNBC cells,and the ICvalues of MDA-MB-468 and MDA-MB-231 cells treated with LR004-VC-MMAE for 72 h were(0.13±0.02)nmol/L and(0.66±0.06)nmol/L,respectively,which were significantly lower than that of cells treated with MMAE[(3.20±0.60)nmol/L,P<0.01,and(6.60±0.50)nmol/L,P<0.001].LR004-VC-MMAE effectively inhibited migration and invasion of MDA-MB-468 and MDA-MB-231 cells.Moreover,LR004-VC-MMAE also killed tumor stem cells in EGFR-positive TNBC cells and impaired their tumorsphere-forming ability.In TNBC xenograft models,LR004-VC-MMAE at 10 mg/kg significantly suppressed tumor growth and achieved complete tumor regression on day 36.Surprisingly,tumor recurrence was not observed until the end of the experiment on day 52.In a mechanistic study,we found that LR004-VC-MMAE significantly induced cell apoptosis and cell cycle arrest at G/M phase in MDAMB-468[(34±5)%vs.(12±2)%,P<0.001]and MDA-MB-231[(27±4)%vs.(18±3)%,P<0.01]cells.LR004-VC-MMAE also inhibited the activation of EGFR signaling and the expression of cancer stemness marker genes such as Oct4,Sox2,KLF4 and EpCAM.Conclusions:LR004-VC-MMAE showed effective antitumor activity by inhibiting the activation of EGFR signaling and the expression of cancer stemness marker genes.It might be a promising therapeutic candidate and provides a potential therapeutic avenue for the treatment of EGFR-positive TNBC.

Potential Toxicological and Cardiopulmonary Effects of PM2,5 Exposure and Related Mortality:Findings of Recent Studies Published during 2003-2013

Air pollution has environmental issue owing become a serious to its diverse harmful effects on the physical and biological environment. According to the Environmental Protection Agency （EPA） and the World Health Organization （WHO）, air pollution affects millions of people worldwide. Hundreds of thousands of deaths each year and a range of diseases, particularly among vulnerable groups （i.e., children, the elderly, and people with special medical conditions）, are attributed to air pollution. These effects are not always caused by single pollutant in the air; rather, they are considered consequences of the multi-pollutants to which people are simultaneously exposed.

Soret和Dufour效应耦合对HL-2A偏滤器靶板氘浓度与温度双扩散的影响

在L/H模放电情况下,考虑Soret和Dufour效应耦合影响,用JD-CF程序研究了HL-2A偏滤器靶板中氘粒子浓度、温度、滞留量随时间变化影响。结果表明,在L/H模放电下,Soret和Dufour效应会对不同靶板材料(RAFM钢/钨)内不同位置处氘浓度分布、温度分布、氘滞留量产生一定影响,其最大变化率约为10%。在H模放电下Soret和Dufour效应对靶板的影响比在L模放电下的更明显,且对RAFM钢的影响比对钨的更明显。该研究结果对研究边缘等离子体输运、聚变堆燃料再循环、氚的滞留及投料量有一定参考价值。

精准扶贫政策的隐性价值评估--基于流动人口的收入溢出效应视角

作为人类一次大规模的准自然实验,中国脱贫攻坚取得全面胜利之后,其政策效应和历史经验需要深入总结。跳出仅聚焦精准扶贫政策效应“显性价值”的传统视角,从更广阔的视域来审视其可能带来的“隐性价值”,评估其“看不见的效应”。基于对脱贫县非贫困户外出流动人口这一非政策群体可能是外溢对象的观察,利用全国流动人口动态监测调查数据,运用双重差分方法评估精准扶贫政策对其收入的外溢效应。研究发现,精准扶贫政策对外流人口具有显著的正向收入溢出效应。群体异质性研究发现,这种外溢存在“马太效应”,高收入流动人口的溢出效应显著高于低收入群体;流入地空间异质性研究结果显示,西部地区获得的外溢效应最小;流出地空间异质性研究结果显示,老家处于村庄或乡镇的人口具有显著的收入溢出效应,而县城及以上区域不显著。机制分析发现,外溢效应可以通过同群影响、东西部地区协作、公共服务完善等渠道产生作用。因此,未来乡村振兴过程中应继续优化传承精神扶贫、区域协作、基础设施建设等农村贫困治理方略。

Effects of natural-cerebrolysin-containing serum on neurotoxicity and synaptogenesis in amyloid-beta 1-40-induced Alzheimer's disease in vitro models

BACKGROUND： Neuronal loss, synapse mutilation, and increasing malnourished axons are pathologically related to Alzheimer＇s disease. Microtubule-associated protein 2 （MAP2） is of importance for neuronal, axonal, and dendritic generation, extension, and stabilization, as well as for the regulation of synaptic plasticity. OBJECTIVE： To investigate the antagonistic effects of natural-cerebrolysin-containing serum on beta amyloid protein 1-40 （Aβ1-40）-induced neurotoxicity from the standpoints of cell proliferation, synaptogenesis, and cytoskeleton formation （MAP2 expression）. DESIGN, TIME AND SETTING： A paralleled, controlled, neural cell, and molecular biology experiment was performed at the Institute of Integrated Chinese and Western Medicine, Shenzhen Hospital, Southern Medical University between February 2006 and April 2008. MATERIALS： PC12 cells, derived from the rat central nervous system, were purchased from Shanghai Institute of Cell Biology, Chinese Academy of Sciences, China. A β1-40 was provided by Sigma, USA. Natural-cerebrolysin was provided by Shenzhen Institute of Integrated Chinese and Western Medicine, China. The natural-cerebrolysin was predominantly composed of Renshen （Radix Ginseng）, Tianma （Rhizoma Gastrodiae）, and Yixingye （Ginkgo Leaf） in a proportion of 1：2：2. Following conventional water extraction technology, an extract （1：20） was prepared. Each gram of extract equaled 20 grams of crude drug. In a total of 12 adult male New Zealand rabbits, six underwent intragastric administration of natural-cerebrolysin extract for 1 month to prepare natural-cerebrolysin-containing serum, and the remaining six rabbits received intragastric administration of physiological saline to prepare normal blank serum. METHODS： An AIzheimer＇s disease in vitro model was induced in PC12 cells using Aβ1-40. The cells were incubated with varying doses of natural-cerebrolysin-containing serum （2.5%, 5%, and 10%）. Normal blank serum-treated PC12 cells served as a blank control group. MAIN OUTCOME MEASURES： Through the use of inverted phase contrast microscope, cell morphology and neurite growth were observed, neurite length was measured, and the percentage of neurite-positive cells was calculated. Cell proliferation rate was determined by MTT assay, and MAP 2 expression was detected by fluorescent immunocytochemistry. RESULTS： Following Aβ1-40 treatments, some PC12 cells were apoptotic/dying, and only a few short neurites were observed. Following interventions with natural-cerebrolysin-containing serum, the PC12 cells proliferated, there was an increased number of neurites, and neurite length was enhanced. After middle- and high-dose natural-cerebrolysin treatments, the percentage of neurite-positive cells, as well as the average length of neurites, was significantly greater than the normal blank serum-treated PC12 cells （P 〈 0.05 or P 〈 0.01）. Compared with the blank control group, MAP2 expression in the Aβ1-40-treated PC12 cells was significantly inhibited, and the cell proliferation rate was significantly decreased （P 〈 0.01）. Following incubations with natural-cerebrolysin-containing serum, MAP2 expression and cell proliferation rate in the PC12 cells were significantly increased in a dose-dependent manner, compared with treatments with blank control serum （P 〈 0.05 or P 〈 0.01 ）. CONCLUSION： Natural-cerebrolysin exhibited antagonistic effects on neurotoxicity in Aβ1-40 induced Alzheimer＇s disease in vitro models. These effects were likely related to cell proliferation and the upregulation of intracellular MAP2 expression.

MiR-183-5p promotes the progression of non-small cell lung cancer through targeted regulation of FOXO1

Objective To investigate miR-183-5p targeting to forkhead box protein O1(FOXO1)and its corresponding effect on the proliferation,migration,invasion,and epithelial-mesenchymal transition(EMT)of non-small cell lung cancer(NSCLC)cells.Methods NSCLC tissues and adjacent normal tissues from 60 patients with NSCLC adenocarcinoma were obtained via pathological biopsy or intraoperative resection.Several cell lines were cultured in vitro,including the human normal lung epithelial cell line BEAS-2B and human NSCLC cell lines A549,SPCA-1,PC-9,and 95-D.miR-183-5p and FOXO1 mRNA expression in tissues and cells were detected by qRT-PCR;the corresponding correlations in NSCLC tissues were analyzed using the Pearson test,and the relationship between miR-183-5p expression and clinicopathological parameters was analyzed.The miR-183-5p-mediated regulation of FOXO1 was verified by bioinformatics prediction alongside double luciferase,RNA-binding protein immunoprecipitation(RIP)assay,and pull-down experiments.A549 cells were divided into control,anti-miR-NC,anti-miR-183-5p,miR-NC,miR-183-5p,miR-183-5p+pcDNA3.1,and miR-183-5p+pcDNA3.1-FOXO1 groups.Cell proliferation,invasion,migration,apoptosis,and cell cycle distribution were detected using an MTT assay,clone formation assay,Transwell assay,scratch test,and flow cytometry,respectively.The expression of EMT-related proteins in the cells was analyzed by western blotting.The effect of miR-185-3p silencing on the development of transplanted tumors was detected by analyzing tumor formation in nude mice.Results miR-183-5p expression was significantly higher in NSCLC tissues and cells than in adjacent normal tissues,whereas FOXO1 mRNA expression was significantly down-regulated.There was a significant negative correlation between miR-183-5p and FOXO1 mRNA in NSCLC tissues(P<0.05).Additionally,the expression of miR-183-5p was significantly correlated with tumor size,tumor differentiation,and tumor-node-metastasis stage in patients with NSCLC(P<0.05).miR-183-5p targeted and inhibited FOXO1 expression.Compared to the anti-miR-NC group,the cell proliferation,scratch healing rate,N-cadherin and vimentin protein expression,and the proportion of S phase cells were significantly lower in the anti-miR-183-5p group,whereas the protein expression of E-cadherin andα-catenin and the proportion of G0/G1 phase cells were significantly higher;additionally,the frequency of colony formation and invasion were significantly lower in the anti-miR-183-5p group(P<0.05).Compared to the miR-NC group,the cell proliferation,scratch healing rate,N-cadherin and vimentin protein expression,and the proportion of S phase cells in the miR-183-5p group were significantly higher,whereas the E-cadherin andα-catenin protein expression and the proportion of G0/G1 phase cells were significantly lower;furthermore,the frequency of colony formation and invasion were significantly higher in the miR-183-5p group(P<0.05).Compared with the miR-183-5p+pcDNA3.1 group,the OD value,scratch healing rate,N-cadherin and vimentin protein expression,and the proportion of S phase cells were significantly lower in the miR-183-5p+pcDNA3.1-FOXO1 group,whereas E-cadherin andα-catenin protein expression and the proportion of G0/G1 phase cells were significantly higher;additionally,the frequency of colony formation and invasion was significantly lower in the miR-183-5p+pcDNA3.1-FOXO1 group(P<0.05).Overall,silencing miR-185-3p inhibited the growth of transplanted tumors and promoted FOXO1 expression.Conclusion Overexpression of miR-183-5p can inhibit apoptosis and promote the proliferation,migration,invasion,and EMT,of NSCLC cells by down-regulating FOXO1 expression.